NCT03308916

Screening At-risk Populations for Hepatic Fibrosis With Non-invasive Markers

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 6,500 (estimated)
• Sponsor: Maja Thiele · Academic / Other
• Sex: All
• Age: 30 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Prospective screening study at Odense University Hospital to assess the effect of transient elastography and other serum and imaging markers of liver fibrosis to detect advanced fibrosis (Kleiner Fibrosis score F3-F4) in patients at risk of non-alcoholic fatty liver disease, alcoholic fatty liver disease, with a control group of participants recruited from the general population.

Detailed description

This protocol describes a prospective screening study at Odense University Hospital, Department of Gastroenterology and Hepatology. The investigators will use liver stiffness measurements with transient elastography to screen 3000 participants from at-risk populations and 3500 participants from the general population for advanced liver fibrosis. At-risk is defined as either (A) a prior or current alcohol overuse (≥21 units/week for men and ≥14 units/week for women) for more than 5 years, or (B) presence of the metabolic syndrome with or without concomitant type 2 diabetes mellitus. The study goal is to evaluate the aptitude of transient elastography as a screening tool for advanced liver fibrosis, based on analyses of benefit, harm, detection rate, technical applicability and prognostic potential. Secondary aims are to compare novel serum markers of liver fibrosis as potential screening tools against transient elastography: The Enhanced Liver Fibrosis test, neoepitope markers of extracellular matrix turnover, cytokeratin-18 based markers and indirect indices of fibrosis from algorithms combining routine liver blood test. Screened participants with elevated liver stiffness (≥8.0 kiloPascal; estimated 400 participants with alcoholic liver disease, 400 participants with non-alcoholic fatty liver disease and 280 participants from the general population) will be investigated with 2-dimensional shear-wave elastography and abdominal ultrasonography and a liver biopsy to confirm or reject presence of advanced fibrosis. All participants with a positive screening elastography will be invited for repeated liver stiffness measurements and serum fibrosis markers after a minimum of one year from inclusion. Participants at risk of alcoholic and non-alcoholic liver disease, independent of liver stiffness measurement at inclusion, will be invited for repeated liver stiffness measurements and serum fibrosis markers after a minimum of one year from inclusion. At-risk participants with elevated liver stiffness measurements at a follow-up visit (\>6.0 kiloPascal) will be offered a liver biopsy, however no earlier than two years after the index biopsy. All participants will be followed for 10 years to assess liver-related outcomes and all-course mortality.

Conditions

• Liver Diseases, Alcoholic
• Fibrosis

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	transient elastography	Ultrasound elastography using shear-wave elastography to measure liver stiffness as a marker of liver fibrosis. Patients with transient elastography above 8.0 kPa selected for liver biopsy to detect advanced liver fibrosis
DIAGNOSTIC_TEST	Enhanced liver fibrosis test	Patented, commercially available algorithm of hyaluronic acid (HA), N-terminal propeptide of collagen type 3 (P3NP) and tissue inhibitor of metalloproteinase 1 (TIMP-1)
DIAGNOSTIC_TEST	Indirect serum markers of liver fibrosis	Diagnostic markers using combination of routine liver biochemistry: age, AST, ALT, platelet count, cholesterol, GGT
DIAGNOSTIC_TEST	Direct serum markers of liver fibrosis	Serum markers that reflect liver extracellular matrix turnover and -accumulation
DIAGNOSTIC_TEST	LiverTRAIL	Software that contain 199 diagnostic algorithms, containing combinations of routine tests: age, AST, albumin, alkaline phosphatase, bilirubin, GGT, INR, platelet count, cholesterol and sodium, and specialist tests: transient elastography and direct serum markers of fibrosis.
DIAGNOSTIC_TEST	Cytokeratin 18	Cytokeratin 18 from liver cell cytoskeleton; when cells undergo apoptosis, caspase-cleaved CK18 is released (M30), whereas full-length CK18 is realised during necrosis (M65)
DIAGNOSTIC_TEST	Omics markers	Markers combining signatures of liver fibrosis and hepatic inflammation from many 'omics technologies

Timeline

• Start date: 2017-10-06
• Primary completion: 2025-12-30
• Completion: 2035-10-30
• First posted: 2017-10-13
• Last updated: 2022-09-01

Locations

1 site across 1 country: Denmark